Regulation of PIPK (phosphatidylinositol phosphate kinase) and PtdIns(4,5)P2 signalling by small G-proteins and their effectors is key to many biological functions. Through selective recruitment and activation of different PIPK isoforms, small G-proteins such as Rho, Rac and Cdc42 modulate actin dynamics and cytoskeleton-dependent cellular events in response to extracellular signalling. These activities affect a number of processes, including endocytosis, bacterial penetration into host cells and cytolytic granule-mediated targeted cell killing. Small G-proteins and their modulators are also regulated by phosphoinositides through translocation and conformational changes. Arf family small G-proteins act at multiple sites as regulators of membrane trafficking and actin cytoskeletal remodelling, and regulate a feedback loop comprising phospholipase D, phosphatidic acid, PIPKs and PtdIns(4,5)P2, contributing to enhancement of PtdIns(4,5)P2-mediated cellular events and receptor signalling. Na+, Kir (inwardly rectifying K+), Ca2+ and TRP (transient receptor potential) ion channels are regulated by small G-proteins and membrane pools of PtdIns(4,5)P2. Yeast phosphatidylinositol 4-phosphate 5-kinases Mss4 and Its3 are involved in resistance against disturbance of sphingolipid biosynthesis and maintenance of cell integrity through the synthesis of PtdIns(4,5)P2 and downstream signalling through the Rom2/Rho2 and Rgf1/Rho pathways. Here, we review models for regulated intracellular targeting of PIPKs by small G-proteins and other modulators in response to extracellular signalling. We also describe the spatial and temporal cross-regulation of PIPKs and small G-proteins that is critical for a number of cellular functions.
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August 2006
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Review Article|
July 27 2006
Supervised membrane swimming: small G-protein lifeguards regulate PIPK signalling and monitor intracellular PtdIns(4,5)P2 pools
Megan Santarius;
Megan Santarius
1
*Program in Molecular and Cellular Pharmacology, University of Wisconsin-Madison, 1300 University Avenue, Madison, WI 53706, U.S.A.
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Chang Ho Lee;
†Department of Pharmacology, College of Medicine, Hanyang University, 17 Hengdang-dong, Seongdong-ku, Seoul, 133-791, South Korea
2To whom correspondence should be addressed (email jennysue@hanyang.ac.kr).
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Richard A. Anderson
Richard A. Anderson
*Program in Molecular and Cellular Pharmacology, University of Wisconsin-Madison, 1300 University Avenue, Madison, WI 53706, U.S.A.
‡Department of Pharmacology, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706, U.S.A.
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Publisher: Portland Press Ltd
Received:
April 13 2006
Revision Received:
June 05 2006
Accepted:
June 07 2006
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 398 (1): 1–13.
Article history
Received:
April 13 2006
Revision Received:
June 05 2006
Accepted:
June 07 2006
Citation
Megan Santarius, Chang Ho Lee, Richard A. Anderson; Supervised membrane swimming: small G-protein lifeguards regulate PIPK signalling and monitor intracellular PtdIns(4,5)P2 pools. Biochem J 15 August 2006; 398 (1): 1–13. doi: https://doi.org/10.1042/BJ20060565
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